SerpinB10, a Serine Protease Inhibitor, Is Implicated in UV-Induced Cellular Response.

Hajnalka Majoros,Imre Miklós Boros,Zoltán G Páhi,Zsuzsanna Ujfaludi,Mónika Mórocz,Lajos Haracska,Barbara N Borsos,Tibor Pankotai

doi:10.3390/ijms22168500

Abstract

UV-induced DNA damage response and repair are extensively studied processes, as any malfunction in these pathways contributes to the activation of tumorigenesis. Although several proteins involved in these cellular mechanisms have been described, the entire repair cascade has remained unexplored. To identify new players in UV-induced repair, we performed a microarray screen, in which we found SerpinB10 (SPB10, Bomapin) as one of the most dramatically upregulated genes following UV irradiation. Here, we demonstrated that an increased mRNA level of SPB10 is a general cellular response following UV irradiation regardless of the cell type. We showed that although SPB10 is implicated in the UV-induced cellular response, it has no indispensable function in cell survival upon UV irradiation. Nonetheless, we revealed that SPB10 might be involved in delaying the duration of DNA repair in interphase and also in S-phase cells. Additionally, we also highlighted the interaction between SPB10 and H3. Based on our results, it seems that SPB10 protein is implicated in UV-induced stress as a “quality control protein”, presumably by slowing down the repair process.

Highlights

Our genome is constantly exposed to endogenous and exogenous sources of damage
To verify the microarray data, we first performed quantitative PCR on Hker E6SFM cells to measure the mRNA level of SPB10 in basal conditions and upon UV irradiation
We revealed an increase in the mRNA level of SPB10 upon UV irradiation in three skinderived cell lines (Hker E6SFM, HaCaT, and A375)

Summary

Introduction

Our genome is constantly exposed to endogenous and exogenous sources of damage. One of them is UV radiation, which has many harmful physiological and biological consequences, such as premature aging, immunosuppression, overactivation of inflammatory processes, DNA damage, and even the activation of apoptosis [1,2]. To rescue the stalled replication machinery, eukaryotic cells have evolved error-prone translesion (TLS) DNA polymerases, which can pass through the lesions To keep these low-fidelity TLS polymerases away from the undamaged DNA, interaction is required between them and the proliferating cell nuclear antigen (PCNA), which serves as a binding platform for proteins involved in the recognition and repair of damage [7,8,9,10,11,12,13]. One of the main steps in the exchange of replicative polymerases to TLS DNA polymerases at stalled replication forks is monoubiquitylation; the activation of PCNA, mediated by Rad and Rad ubiquitin ligases, is a crucial step for successful repair [7,10,14,15,16,17] Any malfunction in these processes can lead to the accumulation of DNA mutations or chromosomal rearrangements or can affect chromosome segregation, resulting in tumorous malformations [18]

Methods

Results

Conclusion